Immune regulation of complement component is being studied in F1 hybrids from matings of normal (homozygous) males and females homozygous for specific genetic defects in single complement components. Specific chronic suppression of the fifth component of complement (C5) has been accomplished in (C5-C5 plus)F1 mice by 1.) neonatal administration of anti antibody and 2.) by neonatal administration of (C5-C5-) parental cells. Antibody induction of suppression of the fourth component of complement (C4) was not accomplished in vivo but can be demonstrated in vitro. It will be determined whether the sixth component of rabbit complement can be similarly suppressed in (C6-C6 plus)F1 animals and whether this affects the expression of C6 allotypes. The major goal of the experiments outlined is to elucidate the mechanisms of regulation of complement components. In vitro and in vivo experiments will be carried out with whole cell populations, fractionated subpopulations and purified antibodies to determine: 1) relevant cell types and their genetic control, 2) the role of antibody and other humoral regulatory factors, 3) the role of the state of immunity of mothers and cell donors and 4) the influence of genetic polymorphism of the complement component being suppressed. Since complement components are relatively homogeneous proteins under simple gentic control, they offer a unique model with which to extend studies of immune regulation into systems consisting of nonlymphoid cell products.